The large number of observations implicating macrophage Fc receptors in the phenomena of adherence and phagocytosis of particles, and antibody-dependent cellular cytotoxicity underline the importance of these receptors in macrophage physiology and function. Yet there is little known about the biochemical nature of these receptors. Mouse macrophages have been recently shown to possess two Fc receptors which differ in specificity and resistance to trypsinization. Mutant clones of mouse macrophage cell lines will be selected by their inability to form rosettes with suitably sensitized erythrocytes. The binding of different mouse IgG subclasses to these clones will be characterized with respect to Ka and number of sites per cell. The differences between the parental and variant phenotypes will then be investigated in a series of biochemical and genetic experiments. Initially, mutant clones will be screened to ascertain if they possess other macrophage markers, such as phagocytosis of latex, rapid adherence to a solid surface, the complement receptor, and secretion of lysozyme and plasminogen activator. By comparison of the surface polypeptides of the parent and variant clones we hope to correlate macrophage function with the detailed structure of the plasma membrane. Labeled plasma membrane proteins of parental and variant clones will be compared using electrophoretic and immunochemical techniques. Finally, isolation of a panel of variant clones makes feasible a genetic study of the steps in synthesis of these receptors and their insertion into the plasma membrane. As a first step, complementation analysis will be used to categorize the variants into groups for further biochemical analysis.